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Human Exposure Sources and Disposition of Perfluoroalkyl Acid Isomers

  • Author / Creator
    Beesoon,Sanjay
  • Perfluoroalkyl acids (PFAAs) are a family of emerging toxicants that are non-biodegradable, and have the potential to bioconcentrate and biomagnify. In an attempt to answer questions about human exposure to PFAAs, and subsequent human disposition of these compounds which have public health implications, four hypothesis-driven and multidisciplinary research projects were conducted. The first project used an isomer-specific LC-MS/MS method to characterize the PFAA isomer signatures in house dust, and whether PFAA isomers could cross the human placenta to different extents. The findings showed that a Canadian population was currently exposed to a mix of both telomer and electrochemical perfluorooctanoate (PFOA), despite the latter having been phased out since 2002. Strong evidence for the preferential transfer of branched perfluorooctanesulfonate (PFOS) and PFOA isomers, compared to linear, was found by comparing 20-paired maternal and cord blood samples. The second project was conducted on a local family of seven individuals, all of whom had exceptionally high serum levels of perfluorohexanesulfonate (PFHxS). A forensic investigation was conducted in the family’s dwelling, and data revealed that the source of the high exposure in this family was the house carpets which had been treated multiple times with Scotchgard™ formulations over a period of 15 years. The pathway of exposure was most-likely through inhalation and ingestion of house dust. A series of in vitro experiments were conducted in a third project to assess the dissociation constants (Kd) of linear and branched PFOA and PFOA isomers. Kd’s of the linear isomers were lower than the branched isomers, and in technical mixtures spiked to serum it was evident that the branched isomers were less bound to serum protein, and thus would be more bioavailable to cross into fetal circulation or be excreted by the kidney. The last research project modeled the transplacental transfer of PFAAs in-vitro using cultured human placental syncytiotrophoblasts. This model confirmed the findings of the first study, to the effect that branched isomers, especially in the case of PFOA, crossed the placental barrier more efficiently than linear molecules, independent of their serum protein binding. Overall, this thesis contributed unique observations from biomonitoring of PFAAs at the isomer-specific level, and follow-up experiments helped to explain these while furthermore contributing to our understanding of how PFAAs are biopersistent in humans.

  • Subjects / Keywords
  • Graduation date
    2014-06
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3SF2MM17
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Medical Sciences- Laboratory Medicine and Pathology
  • Supervisor / co-supervisor and their department(s)
    • Dr Jonathan W Martin
  • Examining committee members and their departments
    • Dr. X. Chris Le; University of Alberta, Department of Laboratory Medicine and Pathology
    • Dr Bernadette Quemerais; University of Alberta, Department of Preventive Medicine
    • Dr Monika Keelan; University of Alberta, Department of Laboratory Medicine and Pathology
    • Dr. Kurunthachalam Kannan; Department of Environmental Health Sciences, School of Public Health, State University of New York, USA
    • Dr. Steve Hrudey; University of Alberta, Department of Laboratory Medicine and Pathology